Enhanced Gene and siRNA Delivery by Polycation-Modified Mesoporous Silica Nanoparticles Loaded with Chloroquine

被引:100
作者
Bhattarai, Shanta Raj [1 ]
Muthuswamy, Elayaraja [2 ]
Wani, Amit [1 ]
Brichacek, Michal [2 ]
Castaneda, Antonio L. [2 ]
Brock, Stephanie L. [2 ]
Oupicky, David [1 ]
机构
[1] Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI 48202 USA
[2] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA
关键词
gene delivery; mesoporous; nanoparticles; polycation; silica; siRNA; DRUG-DELIVERY; IN-VIVO; CANCER-CELLS; CONTROLLED-RELEASE; MOLECULAR-WEIGHT; DNA DELIVERY; PLASMID DNA; NANOSPHERE; CYTOTOXICITY; VITRO;
D O I
10.1007/s11095-010-0245-0
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids. The surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly(2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH. The results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The co-delivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ. PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.
引用
收藏
页码:2556 / 2568
页数:13
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